Shan J, Benishin C G, Lewanczuk R Z, Pang P K
Department of Physiology, University of Alberta, Edmonton, Canada.
J Cardiovasc Pharmacol. 1994;23 Suppl 2:S1-8.
The present studies investigated the effect of parathyroid hypertensive factor (PHF) on intracellular calcium regulation in VSMC. Nifedipine inhibited the hypertensive effect of PHF in Sprague-Dawley (SD) rats in vivo. PHF amplified the L-type calcium current in vascular smooth-muscle cells (VSMCs) isolated from SD rat tail artery. PHF potentiated the tension induced by norepinephrine (NE) in the presence of normal added CaCl2 and inhibited the tension dependent on Ca2+ release from intracellular calcium store(s) induced by NE in SD rat tail artery helical strips. PHF potentiated the intracellular free calcium concentration ([Ca2+]i) increment induced by KCl in cultured VSMCs from SD rat tail artery. All of the in vitro cellular calcium effects of PHF temporally correlated with its delayed hypertensive effect in vivo. PHF did not affect the accumulation of inositol phosphates in SD rat tail artery. Infusion of theophylline blunted the hypertensive effect of PHF in SD rats, suggesting that PHF may stimulate phosphodiesterase (PDE) activity. We suggest that PHF may potentiate the effects of other vasoconstrictors on calcium channels and increase [Ca2+]i, which would then lead to an increase in the responsiveness of the VSMC to other vasoconstrictors, and therefore an increase in blood pressure. The action of PHF may involve stimulation of PDE activity.
本研究调查了甲状旁腺高血压因子（PHF）对血管平滑肌细胞（VSMC）内钙调节的影响。硝苯地平在体内可抑制PHF对Sprague-Dawley（SD）大鼠的升压作用。PHF可增强从SD大鼠尾动脉分离的血管平滑肌细胞（VSMC）中的L型钙电流。在添加正常CaCl2的情况下，PHF可增强去甲肾上腺素（NE）诱导的张力，并抑制SD大鼠尾动脉螺旋条中依赖于细胞内钙库释放Ca2+的NE诱导的张力。PHF可增强SD大鼠尾动脉培养的VSMC中KCl诱导的细胞内游离钙浓度（[Ca2+]i）升高。PHF在体外对细胞钙的所有作用在时间上与其在体内的延迟升压作用相关。PHF不影响SD大鼠尾动脉中肌醇磷酸的积累。输注茶碱可减弱PHF对SD大鼠的升压作用，提示PHF可能刺激磷酸二酯酶（PDE）活性。我们认为，PHF可能增强其他血管收缩剂对钙通道的作用并增加[Ca2+]i，进而导致VSMC对其他血管收缩剂的反应性增加，从而使血压升高。PHF的作用可能涉及对PDE活性的刺激。
